› 5tc4

X-ray diffraction
1.89Å resolution

Crystal structure of human mitochondrial methylenetetrahydrofolate dehydrogenase-cyclohydrolase (MTHFD2) in complex with LY345899 and cofactors

Released:
DOI: 10.2210/pdb5tc4/pdb
PDB entry 5tc4 coloured by chain, front view.
PDB entry 5tc4 coloured by chain, side view.
PDB entry 5tc4 coloured by chain, top view.
Source organism: Homo sapiens
Primary publication:
Crystal Structure of the Emerging Cancer Target MTHFD2 in Complex with a Substrate-Based Inhibitor.
Gustafsson R, Jemth AS, Gustafsson NM, Färnegårdh K, Loseva O, Wiita E, Bonagas N, Dahllund L, Llona-Minguez S, Häggblad M, Henriksson M, Andersson Y, Homan E, Helleday T, Stenmark P
Cancer Res 77 937-948 (2017)
PMID: 27899380

Function and Biology Details

Reactions catalysed: 
5,10-methylenetetrahydrofolate + NAD(+) = 5,10-methenyltetrahydrofolate + NADH
5,10-methenyltetrahydrofolate + H(2)O = 10-formyltetrahydrofolate
Biochemical function:
Biological process:
Cellular component:
Sequence domains:

Structure analysis Details

Assembly composition:
homo dimer (preferred)
Assembly name:
PDBe Complex ID:
PDB-CPX-146835 (preferred)
Entry contents:
1 distinct polypeptide molecule
Macromolecule:
Bifunctional methylenetetrahydrofolate dehydrogenase/cyclohydrolase, mitochondrial Chain: A
Molecule details ›
Chain: A
Length: 316 amino acids
Theoretical weight: 34.31 KDa
Source organism: Homo sapiens
Expression system: Escherichia coli BL21(DE3)
UniProt:
  • Canonical: P13995 (Residues: 36-350; Coverage: 90%)
Gene names: MTHFD2, NMDMC
Sequence domains:
Structure domains:

Ligands and Environments


Cofactor: Ligand NAD 1 x NAD
2 bound ligands:
Ligand L34 1 x L34
Ligand PO4 1 x PO4
No modified residues

Experiments and Validation Details

Entry percentile scores
X-ray source: ESRF BEAMLINE MASSIF-3
Spacegroup: I4
Unit cell:
a: 74.323Å b: 74.323Å c: 98.62Å
α: 90° β: 90° γ: 90°
R-values:
R R work R free
0.165 0.163 0.212
Expression system: Escherichia coli BL21(DE3)

Quick links

Citations

13 review citations

Formate metabolism in health and disease.
Pietzke et al. (2020)
12 more

10 mentions without citation

A Review of Small-Molecule Inhibitors of One-Carbon Enzymes: SHMT2 and MTHFD2 in the Spotlight.
Cuthbertson et al. (2021)
9 more